JPS6187662A - Production of indoles - Google Patents

Abstract

PURPOSE:To produce an indole compound useful as a raw material of perfume and amino acid such as tryptophan, etc., in high yield, economically in an industrial scale, by the catalytic thermal reaction of 2-(o-aminoaryl)ethanol in the presence of a specific catalyst. CONSTITUTION:An indole compound can be produced by the catalytic reaction of the 2-(o-aminoaryl)ethnol of formula I (X is H, 1-12C alkyl or alkoxy, halogen, or OH; R<1> and R<2> are H, 1-4C alkyl, 5-6C cycloalkyl or 6-10C aryl) or the indoline compound of formula II (R<3> and R<4> are same as R<1> and R<2>) in the presence of a catalyst containing a platinum-group metal and an alkali metal, e.g. Pd.K-C, Ru.K-C, etc., at 130-300 deg.C for 0.1-20hr under atmospheric pressure, or in some case, under reduced pressure or positive pressure. EFFECT:The objective compound can be produced from an easily available raw material at a low catalyst cost.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to 2-(o-aminoaryl)ethanols 4
Chirui uses indolines as raw materials and relates to a method for producing indoles from these.

According to the method of the present invention, indoles can be industrially advantageously produced in good yield.

Indoles include fragrances, amino acids such as tryptophan,
It is an industrially useful substance as a raw material for polymer stabilizers, etc.

Prior Art German Patent No. 606,027 discloses a method for obtaining indolines and/or indoles by subjecting 2-(0-aminoaryl)ethanols to a catalytic gas phase reaction. Catalysts that can be used in this method include Cu, Co, and Mi.

AgXFle, PdXPt, MoXwlpb, M
n, At.

Ti5Zr, Cr, Th, etc. are exemplified, and (::uCOa) is described as a specific example that can mainly produce indole. However, these catalysts are not industrially satisfactory due to a decrease in activity. There wasn't.

On the other hand, as a method for producing indoles by dehydrogenation reaction using indolines as a raw material, for example, a method using a Raney nickel catalyst (Acta (him).

Acad, Sci, Hung,, ■, 167 (
1967)), a method using a chromium oxide or copper-chromium catalyst [Roczniki, Chem, 38, 5
07 (1964)) Method using manganese dioxide catalyst (
J, Org, Chern, L Yu, 1540 (19
64)) are known.

However, these cases also had the drawback of low yield and selectivity.

Furthermore, JP-A No. 52-142063 discloses that indolines or 142-(o-aminoaryl)ethanols are treated with at least one kind selected from the group consisting of nitric acid, nitrous acid, acidic sulfates, and acidic sulfites. A method for producing indoles by heating with an acidic compound is disclosed.

However, this method also requires a large amount of catalyst, making it difficult to call it an industrial production method.

Problems to be Solved by Akira The inventors of the present invention aimed to find an industrially advantageous method for producing indoles at low catalyst costs and high yields using readily available and inexpensive raw materials. ,
The present invention was completed after a wide range of studies including raw materials and media.

ME! The present invention provides a method for producing indoles by catalytically reacting 2-(0-aminoaryl)ethanols or indolines in the presence of a catalyst containing a platinum metal and an alkali metal. The present invention provides a method for producing indoles, which involves heating.

Detailed Description of the Invention The 2-(O-aminoaryl)ethanols or indolines used in the method of the present invention have the general formula (
1), or a compound represented by the general formula [厘]. In the above formula, X is hydrogen, C1
-12 alkyl group, C5-12 alkoxy group, halogen atom or hydroxyl group, R'', R'', R'' and W are each hydrogen, 01-4 alkyl group, Cs~
6 cycloalkyl groups and C6-1o aryl groups, which may be the same or different.

Specific examples of the 2-(O-aminoaryl)ethanols represented by the above general formula (1) include 2-(o-
aminophenyl)ethanol, 2-(2-amino-5-
isopropylphenyl)ethanol, 2-(2-amino-5-tert-butylphenyl)ethanol, 2-(
2-amino-5-)fluorophenyl)ethanol, 2
-(2-amino-5-hydroxyphenyl)ethanol, 2-(2-amino-3-methoxyphenyl)ethanol, 2-(2-amino-6-methoxyphenyl)ethanol, 2-(2-amino-6- methoxyphenyl)ethanol, l-methyl-2-(O-aminophenyl)ethanol, 1-ethyl-2-(o-aminophenyl)ethanol, 1-isopropyl-2-(o-aminophenyl)ethanol, 1-cyclohexyl -2-(o-7minophenyl)ethanol, 2-(2-amino-6-benzyloxyphenyl)ethanol, 2-(2-amino-5-
benzyloxyphenyl)ethanol, 1-phenyl-2
-(o-aminophenyl)ethanol, 2-methyl-2
-(o-aminophenyl)ethanol, 2^phenyl-
Examples include 2-(o-ami/phenyl)ethanol and 1-phenyl-2-(2-amino-5-methoxyphenyl)ethanol.

Further, specific examples of indolines represented by the general formula [厘] include indoline, 2-methylindoline,
3-methylindoline, 4-methylindoline, 5-methylindoline, 6-methylindoline, 7-methylindoline, 2,3-dimethylindoline, 2,5-dimethylindoline, 3゜6-dimethylindoline, 2-ethylindoline , 3-x5-luintrin, 5-ethylindoline, 2-tert-butylindoline, 5-
tert-butylindoline, 2-cyclohexylindoline, 2-phenylindoline, 3-phenylindoline, 5-hydroxyindoline, 5-methoxyindoline, 5-chloroindoline, 4-hydroxyindoline, 6-hydroxyindoline, 4-methoxyindoline, 6-methoxyindoline Examples include 4-penzyloxyindoline, 6-benzyloxyindoline, 5-benzyloxyindoline, and the like.

Used in the method of the present invention! Soot contains platinum group metals such as platinum, palladium, rhodium, and ruthenium, and alkali metals such as lithium, sodium, potassium, rubidium, and cesium. Among these catalyst components, palladium is selected as the platinum group metal, potassium or sodium is selected as the alkali metal, and when a catalyst containing a combination of these is used,
This is preferred because the desired indoles can be obtained in good yield.

Although the catalyst containing the above-mentioned catalyst component is used as it is in the reaction for producing indoles, it is preferably used by supporting the above-mentioned catalyst component on a carrier. .

As the carrier, metal oxides, activated carbon, carbon black, graphite, metal phosphates, metal carbonates, metal phosphates, etc. are used. Specific examples include various composite oxides such as activated carbon, carbon black, alumina, silica, silica-alumina, titania, geriatric earth, titania-silica, titania-magnesia, silica-magnesia, and alumina-titania. Among these, activated carbon is a particularly preferred carrier.

The platinum group metals and alkali gold R contained as active components in the catalyst used in the method of the present invention are not particularly limited in their state of existence before, during, or after use as a catalyst in the reaction. , for example platinum group metals are in the metal, metal oxide or metal halide state, alkali gold, gold &! , metal oxide, metal carbonate, metal sulfate, metal halide, or metal phosphate.

The catalyst used in the method of the present invention contains the above-mentioned platinum group metals and alkali metals, but an additive may be added to these medium components.

Substances to be added to this third group include alkaline earth metals, Group 1B metals such as copper and silver, Group II metals such as iron, cobalt, and nickel, and Group II alloys such as manganese (1, chromium, molybdenum, tungsten, etc.). Examples include Group 4 metals such as vanadium, Group V metals such as tin and lead, Group 1B metals such as zinc and cadmium, and Hmm alloys such as boron.

Users of the above soot should add 0.00001 to 10 moles, preferably 0.00001 to 10 moles of platinum alloy or 1 mole of 2-(o-aminoaryl)ethanol or indoline as raw materials.
0001-1 mol, alkali metal 0.00002-2
It is used in an amount of 0 mol, preferably 0.0002 to 2 mol.

In the method of the present invention, the desired indoles can be produced in good yield simply by heating the raw material 2-(o-aminoaryl)ethanols or indolines in the presence of the above catalyst.

This heating temperature is usually 130 to 300°C, preferably 1
The temperature is 50-250°C. If the degree of bowing is higher than 300°C, side reactions will proceed rapidly, and if the temperature is lower than 6130°C, which is undesirable, the reaction rate will be slow and the reaction time will be long. Therefore, the reaction time is not particularly limited, but is generally about 0.1 to about 20 hours.

The reaction should be carried out under pressure such that at least a portion of the 2-(O-aminoaryl)ethanols or indolines remains in the liquid phase. Generally, it is carried out under atmospheric pressure, but it can also be carried out under reduced pressure or increased pressure, which satisfies the above conditions.

It is preferable to stir the reaction solution, and it is preferable to carry out stirring by ordinary stirring R or by blowing in an inert gas such as nitrogen.

This tends to improve the selectivity and the like.

The reaction proceeds satisfactorily without a solvent. While water and hydrogen produced in the reaction are removed from the reaction system, the produced indoles can also be taken out continuously. In this case, it is preferable to continuously supply the raw material to the reactor.

Although this reaction proceeds satisfactorily even in the presence of a solvent, it is preferable to use a solvent having a boiling point higher than that of the indoles produced.

3" button i The method of the present invention will be specifically explained below with examples and comparison columns. Note that the yields in the examples and comparative examples are based on the 2-(o-aminoaryl)ethanol used. Or mole % based on indolines.

Example 1 2-(o-aminophenyl)ethanol 2 was placed in a Pyrex flask equipped with simple distillation equipment (distillation head, Liebig, adapter, receiver) and nitrogen gas blowing tube.
f (14.6 mmol), Engelhard Japan! 5
%Pd-carbon (5%Pd-C) catalyst and further 2C
By supporting 5 wt% of Oa, Pd-
K-C: 0.3? (Pd20.13 mmol)
Add a magnetic stirrer and heat the oil bath to 185-195.
The reaction mixture was heated to .degree. C. and reacted for 4 hours while blowing nitrogen gas into the flask. After the reaction, collect the product with ethanol,
Indole was quantified by gas chromatography analysis. As a result, the 2-(0-aminophenyl)ethanol conversion rate was 100% and the indole yield was 88.8%.

Very few by-products were confirmed by gas chromatography.

Example 2 The amount of -C was 0.159 (, Pd:
An experiment was carried out in the same manner as in Example 1, except that the amount of 2-(0-aminophenyl) ethanol was changed to 93.9% and the indole yield was 75.4%.

Example 3 The amount of 2CO3 supported on the catalyst Pd-K-C was
wt%, and the amount of the Pd--C catalyst used was 0.
1f (Pd: 0.042 mmol), and further 1.36 f of the raw material 2-(0-aminophenyl)ethanol.
An experiment was conducted in the same manner as in Example 1 except that the amount of 2-(o-aminophenyl)ethanol was 91.9%, and the indole yield was 68.6%.
Met.

Example 4 The reaction was carried out in the same manner as in Example 1 (2-(o-aminophenyl)ethanol conversion rate 100%, indole yield 86
．． 2%] The reaction solution was suction filtered and washed with ethanol to recover the catalyst.

The reaction was carried out in the same manner as in Example 1 except that this catalyst was used, resulting in a 2-(0-aminophenyl)ethanol conversion of 100% and an indole yield of 91.6%.

Example gAJ5 After carrying out the same reaction as in Example 1, the catalyst was recovered and reused four times in the same manner as in Example 4. The result of the fourth reaction was a 2-(0-aminophenyl)ethanol conversion rate of 8.
The yield of indole was 54.9%. The catalyst was recovered from this reaction solution by the same post-treatment method as in Example 4, and 0.249 was obtained as recovered catalyst.

Add W K2CO3 to this recovered catalyst again at 12+N1 (5
(vt%) was supported and catalyst regeneration was carried out. An experiment was conducted in exactly the same manner as in Actual Ti Series 1 except that this regenerated catalyst was used, and the conversion rate of 2-(o-aminophenyl)ethanol was 10.
0%, and the indole yield was 87.7%.

Example 6 Using 2f of n-eicosane as a solvent, 2-(0-
aminophenyl) ethanol 2f15%Pd-C5
-CO03f was added to Pd- containing 2CO3 at wt%, and the oil bath was heated to 185-19% using the same experimental apparatus as in Example 1.
After heating to 5℃ and reacting by blowing N2 for 1 hour, N2
The indole produced was distilled out by vigorously blowing.

When the distilled product was dissolved in ethanol and analyzed by gas chromatography, the conversion rate of 2-(o-aminophenyl)ethanol was 100%, and the indole yield was 88%.
．． It was 3%.

Examples 7 to 10 Reactions were carried out in the same manner as in Example 1, except that the catalysts shown in Table 1 were used.

The reaction results are shown in Table 1.

Table 1 Comparative Example 1 Two Pyrex flasks equipped with a Dimroth condenser
-(O-aminophenyl)ethanol 1.37SF (1
0 mmol), potassium sulfate 0.95 F (7 mmol), a magnetic stirrer, and 22
The reaction was carried out for 1 hour at 0°C. The resulting reaction mixture was neutralized in a sodium carbonate water bath overnight, extracted with ether, and the ether layer was analyzed with a gas chromatograph to quantify indole, and the yield of indole was 6.2%. Ta. Note that the indoline yield was 8.2%.

Comparative Example 2 A reaction was carried out in the same manner as in Example 1, except that a catalyst in which 12% copper oxide was supported as copper on gamma-alumina (T-317J, manufactured by Nissan Girdler) was used.

As a result, the indole yield was 4.4%, and the indoline yield was 36%.
．． 6%.

Patent Applicant: Light Distillates New Application Development Technology Research Association Agent Patent Attorney Hidetoshi Furukawa Attorney Patent Attorney Masahisa Hase Procedural Amendment J (Voluntary) November 13, 1980 Commissioner of the Patent Office Michibe Uga L Case description Patent Application No. 209299, filed in 1982 New Application Development Technology Research Association Address of Agent: 2-5-2 Marunouchi, Chiyoda-ku, Tokyo & Subject of Amendment Detailed Description of the Invention in Book Mji Column a, Contents of Amendment (1) Page 2 of the Specification Line 8 says “MiJ” [Ni
Correct J (2) Insert the following sentence between page 3, line 12 and line 13 of the specification.

[Furthermore, f'r, o in Japanese Patent Application Laid-Open No. 52-85165
- The gas-phase reaction method (Japanese Patent Publication No. 49-20778) using (2-nitrophenyl)ethanol as a raw material to produce indole in one step was not industrially satisfactory due to rapid catalyst deterioration. By keeping o-(2-nitrophenyl)ethanol in a liquid state and carrying out a heating reaction in the presence of hydrogen and a reducing catalyst, indole can be produced in one step while maintaining its function for a long time using a small amount of catalyst. However, according to the examples, a large amount of catalyst is required when the catalyst is used repeatedly, and the indole yield per catalyst unit is not sufficient. Moreover, according to the results of additional tests conducted by the present inventors, the yield of indole was low and the method was not satisfactory as a one-shot method. (See Reference Examples 1 to 3)" (3) Delete "metal" from page 8, line 16 of the specification.

(4) The following experimental example is added after Comparative Example 2 on page 16 of the specification.

Comparative Example 3 The reaction was carried out in the same manner as in Example 1, except that 5% Pd-carbon (5% Pd-C) 0.3 f manufactured by Nippon Engelhard Co., Ltd. was used as a catalyst. The conversion rate of ethanol (0-aminophenyl) was 77.3%, and the indole yield was 47.5%.

Reference example 1 2-(O-nitrophenyl)ethanol 4.45 f (26.6 mmol) in an autoclave with a capacity of 120 d
, dioxane 15d and Nippon Engelhard 5%
After charging Ru-carbon 0.549 and replacing the inside of the system with hydrogen, the pressure was increased to 20 #/d, and the reaction was carried out with stirring at 200° C. for 1 hour.

IN result of product analysis by gas chromatography, 2
- (o-nitrophenyl)ethyl/-ol conversion rate xoo%
The indole yield based on 2-(o-nitrophenyl)ethanol was 13.8%.

Reference Example 2 An experiment similar to Reference Example 1 was conducted except that the catalyst was changed to 5% Rh-carbon 0.589 manufactured by Yokozawa Chemical Industry Co., Ltd. and the reaction temperature was changed to 250°C. The /-ole conversion rate was 100%, and the indole yield was 41.4%.

Reference example 3 Catalyst made by Japan Engel Nord! ! ! The same experiment as in Reference Example 2 was conducted except that the amount of 5% Pd-carbon was changed to 0.59 t and the incubation time was changed to 1.5 hours. The yield was 39.2%. "that's all

Claims (1)

[Claims] (1) A method for producing indoles by catalytically reacting 2-(o-aminoaryl)ethanols or indolines, characterized by heating in the presence of a catalyst containing a platinum group metal and an alkali metal. A method for producing indoles.